Our specific aims are: I. To determine whether essential fatty acids when mobilized from adipose tissue are spared an oxidative fate and sequestered by tumor cells (as suggested recently by Kitada et al.); II. To determine the pathways and quantitative contribution of plasma very low density lipoprotein triglyceride fatty acids (VLDL-TGFA), especially essential TGFA, to various forms of mouse and rat carcinomas; and III. To determine the mechanism(s) and molecular basis of the defect that we have found in VLDL-TGFA removal from plasma in mice bearing EAT and to determine whether this defect is common to other forms of cancers in rodents. We shall use in vivo tracers and multicompartmental analysis of kinetic data obtained initially from cancer-bearing mice (solid Ehrlich-Lettre tumors in Swiss-Webster mice and virus-induced lymphomas in AKR mice) to achieve the first two specific aims. The incorporation of labeled essential and non-essential FA into breath 14CO2 and into tumor cell lipids will be studied after administration of 5 tracers (in separate groups of cancerous mice): FEA i.v., VLDL-TGFA, i.v., chylomicron-TGFA, i.v., adipose tissue-TGFA (labeled in situ) and transplanted, labeled adipose tissue. We shall try to integrate the data into a consistent model, one which might explain certain discrepancies between our earlier results and those published from other laboratories, and which might give a clearer understanding of essential FA transport from host to solid tumors. Other tumor-host models will be studied subsequently and under various nutritional conditions. In addition, lipoprotein lipase activity, and its regulation, and properties of VLDL in cancer-bearing rodents will be studied in an attempt to determine the basis of defective VLDL-TG clearance that occurs in mice with Ehrlich ascites carcinoma. We shall also try to determine, using Triton WR-1339 and tracer techniques (labeled VLDL-TG, i.v.), whether the latter defect occurs in other forms of experimental carcinomas (mice and rats). Our long-term objectives are to interrupt, if possible, the flow of essential fatty acids to cancer cells from the host and to develop strategies for preventing cancer-induced cachexia in the host.